Inhibitory effects of gallic acid and quercetin on UDP-glucose dehydrogenase activity.
We have examined polyphenols as potential inhibitors of UDP-glucose dehydrogenase (UGDH) activity. Gallic acid and quercetin decreased specific activities of UGDH and inhibited the proliferation of MCF-7 human breast cancer cells. Western blot analysis showed that gallic acid and quercetin did not affect UGDH protein expression, suggesting that UGDH activity is inhibited by polyphenols at the post-translational level. Kinetics studies using human UGDH revealed that gallic acid was a non-competitive inhibitor with respect to UDP-glucose and NAD+. In contrast, quercetin showed a competitive inhibition and a mixed-type inhibition with respect to UDP-glucose and NAD+, respectively. These results indicate that gallic acid and quercetin are effective inhibitors of UGDH that exert strong antiproliferative activity in breast cancer cells.
Hwang
Eun Young
EY
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
Huh
Jae-Wan
JW
Choi
Myung-Min
MM
Choi
Soo Young
SY
Hong
Hea-Nam
HN
Cho
Sung-Woo
SW
D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005707:Gallic Acid / Q000494:pharmacology*; D006801:Humans; D009243:NAD / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009243:NAD; D005707:Gallic Acid; D011794:Quercetin; D014533:Uridine Diphosphate Glucose Dehydrogenase; D014532:Uridine Diphosphate Glucose